Disposition and metabolism in 1-(2-chloroethyl)-3-(2',3',4'-tri-o-acetyl, ribopyranosyl)-1-nitrosourea in rats.
The antineoplastic activity in animals of 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl, ribopyranosyl)-1-nitrosourea (RPCNU) has been widely demonstrated. The present study deals with the disposition and the metabolism of three 14C-labeled species of RPCNU. The chemical plasma half-life of the drug was less than 5 min. Within the first min after injections, most of the radioactivity derived from ethyl-14C groups were recovered as volatile products. Among these, 2-chloroethanol was identified as a main component. Analysis of labeled species in urine after administration of [ethyl-14C]RPCNU showed that thiodiacetic acid and its sulfoxide were major metabolites of RPCNU (62% of the urinary radioactivity). Traces of N-acetylcarboxymethyl- and N-acetylhydroxyethylcysteine) were also detected. The only labeled species concentrating in particular tissues was that carrying the chloroethyl moiety. Uptake to high levels of [ethyl-14C]RPCNU did occur in liver, kidney, pancreas, thymus, and Harder's gland.
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000818:Animals; D001646:Bile / Q000378:metabolism; D002233:Carbocysteine / Q000031:analogs & derivatives / Q000652:urine; D002245:Carbon Dioxide / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005023:Ethylene Chlorohydrin / Q000378:metabolism; D005243:Feces / Q000032:analysis; D006207:Half-Life; D007274:Injections, Intraperitoneal; D008297:Male; D009607:Nitrosourea Compounds / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013864:Thioglycolates / Q000652:urine; D014018:Tissue Distribution
D009607:Nitrosourea Compounds; D013864:Thioglycolates; D002245:Carbon Dioxide; C031104:N-acetyl-S-(2-hydroxyethyl)cysteine; C020699:N-acetyl-S-(2-carboxymethyl)cysteine; C010518:thiodiacetic acid; C023479:ICIG 1163; D002233:Carbocysteine; D005023:Ethylene Chlorohydrin; D000111:Acetylcysteine